Genome-wide association study of seasonal affective disorder

Kwo Wei David Ho; Shizhong Han; Jakob V. Nielsen; Dubravka Jancic; Benjamin Hing; Jess Fiedorowicz; Myrna M. Weissman; Douglas F. Levinson; James Bennett Potash

doi:10.1038/s41398-018-0246-z

Genome-wide association study of seasonal affective disorder

School of Medicine

Research output: Contribution to journal › Article

Original language	English (US)
Article number	190
Journal	Translational Psychiatry
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41398-018-0246-z
Publication status	Published - Dec 1 2018

ASJC Scopus subject areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

Cite this

Ho, K. W. D., Han, S., Nielsen, J. V., Jancic, D., Hing, B., Fiedorowicz, J., ... Potash, J. B. (2018). Genome-wide association study of seasonal affective disorder. Translational Psychiatry, 8(1), [190]. https://doi.org/10.1038/s41398-018-0246-z

@article{255248fc8576478b9c0799206b0c2ba4,

title = "Genome-wide association study of seasonal affective disorder",

abstract = "Family and twin studies have shown a genetic component to seasonal affective disorder (SAD). A number of candidate gene studies have examined the role of variations within biologically relevant genes in SAD susceptibility, but few genome-wide association studies (GWAS) have been performed to date. The authors aimed to identify genetic risk variants for SAD through GWAS. The authors performed a GWAS for SAD in 1380 cases and 2937 controls of European-American (EA) origin, selected from samples for GWAS of major depressive disorder and of bipolar disorder. Further bioinformatic analyses were conducted to examine additional genomic and biological evidence associated with the top GWAS signals. No susceptibility loci for SAD were identified at a genome-wide significant level. The strongest association was at an intronic variant (rs139459337) within ZBTB20 (odds ratio (OR) = 1.63, p = 8.4 × 10−7), which encodes a transcriptional repressor that has roles in neurogenesis and in adult brain. Expression quantitative trait loci (eQTL) analysis showed that the risk allele “T” of rs139459337 is associated with reduced mRNA expression of ZBTB20 in human temporal cortex (p = 0.028). Zbtb20 is required for normal murine circadian rhythm and for entrainment to a shortened day. Of the 330 human orthologs of murine genes directly repressed by Zbtb20, there were 32 associated with SAD in our sample (at p < 0.05), representing a significant enrichment of ZBTB20 targets among our SAD genetic association signals (fold = 1.93, p = 0.001). ZBTB20 is a candidate susceptibility gene for SAD, based on a convergence of genetic, genomic, and biological evidence. Further studies are necessary to confirm its role in SAD.",

author = "Ho, {Kwo Wei David} and Shizhong Han and Nielsen, {Jakob V.} and Dubravka Jancic and Benjamin Hing and Jess Fiedorowicz and Weissman, {Myrna M.} and Levinson, {Douglas F.} and Potash, {James Bennett}",

year = "2018",

month = "12",

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doi = "10.1038/s41398-018-0246-z",

language = "English (US)",

volume = "8",

journal = "Translational Psychiatry",

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T1 - Genome-wide association study of seasonal affective disorder

AU - Ho, Kwo Wei David

AU - Han, Shizhong

AU - Nielsen, Jakob V.

AU - Jancic, Dubravka

AU - Hing, Benjamin

AU - Fiedorowicz, Jess

AU - Weissman, Myrna M.

AU - Levinson, Douglas F.

AU - Potash, James Bennett

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Family and twin studies have shown a genetic component to seasonal affective disorder (SAD). A number of candidate gene studies have examined the role of variations within biologically relevant genes in SAD susceptibility, but few genome-wide association studies (GWAS) have been performed to date. The authors aimed to identify genetic risk variants for SAD through GWAS. The authors performed a GWAS for SAD in 1380 cases and 2937 controls of European-American (EA) origin, selected from samples for GWAS of major depressive disorder and of bipolar disorder. Further bioinformatic analyses were conducted to examine additional genomic and biological evidence associated with the top GWAS signals. No susceptibility loci for SAD were identified at a genome-wide significant level. The strongest association was at an intronic variant (rs139459337) within ZBTB20 (odds ratio (OR) = 1.63, p = 8.4 × 10−7), which encodes a transcriptional repressor that has roles in neurogenesis and in adult brain. Expression quantitative trait loci (eQTL) analysis showed that the risk allele “T” of rs139459337 is associated with reduced mRNA expression of ZBTB20 in human temporal cortex (p = 0.028). Zbtb20 is required for normal murine circadian rhythm and for entrainment to a shortened day. Of the 330 human orthologs of murine genes directly repressed by Zbtb20, there were 32 associated with SAD in our sample (at p < 0.05), representing a significant enrichment of ZBTB20 targets among our SAD genetic association signals (fold = 1.93, p = 0.001). ZBTB20 is a candidate susceptibility gene for SAD, based on a convergence of genetic, genomic, and biological evidence. Further studies are necessary to confirm its role in SAD.

AB - Family and twin studies have shown a genetic component to seasonal affective disorder (SAD). A number of candidate gene studies have examined the role of variations within biologically relevant genes in SAD susceptibility, but few genome-wide association studies (GWAS) have been performed to date. The authors aimed to identify genetic risk variants for SAD through GWAS. The authors performed a GWAS for SAD in 1380 cases and 2937 controls of European-American (EA) origin, selected from samples for GWAS of major depressive disorder and of bipolar disorder. Further bioinformatic analyses were conducted to examine additional genomic and biological evidence associated with the top GWAS signals. No susceptibility loci for SAD were identified at a genome-wide significant level. The strongest association was at an intronic variant (rs139459337) within ZBTB20 (odds ratio (OR) = 1.63, p = 8.4 × 10−7), which encodes a transcriptional repressor that has roles in neurogenesis and in adult brain. Expression quantitative trait loci (eQTL) analysis showed that the risk allele “T” of rs139459337 is associated with reduced mRNA expression of ZBTB20 in human temporal cortex (p = 0.028). Zbtb20 is required for normal murine circadian rhythm and for entrainment to a shortened day. Of the 330 human orthologs of murine genes directly repressed by Zbtb20, there were 32 associated with SAD in our sample (at p < 0.05), representing a significant enrichment of ZBTB20 targets among our SAD genetic association signals (fold = 1.93, p = 0.001). ZBTB20 is a candidate susceptibility gene for SAD, based on a convergence of genetic, genomic, and biological evidence. Further studies are necessary to confirm its role in SAD.

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10.1038/s41398-018-0246-z